Implanting and fixing a flexible probe for administering a medical therapy at a treatment site within a patient&#39;body

ABSTRACT

A plurality of embodiments for a flexible probe used to provide photodynamic therapy (PDT) and to effect other medical procedures at an internal treatment site inside a patient&#39;s body. Each of the embodiments of the flexible probe (100, 108, 130, 158, 182, 190, 220, 280, 370, 390, 440, 460, 520) includes a flexible substrate (102, 184, 196, 222, 250, 282, 412, 462, 482, 502, 522) on which are disposed conductive traces (414, 466, 468, 488, 490, 504, 506, 524, 526) electrically connected to leads through which electrical current and signals are conveyed. A plurality of light sources (104, 192, 256, 286, 418, 436, 470, 492, 508, 542) or other micro-electronic circuits are connected to the conductive traces and mounted on the flexible substrate. Each of the embodiments of the flexible probes is enclosed within a transparent, biocompatible polymer envelope (106, 110, 464, 522). Due to the characteristic elastic properties of the flexible substrate, the flexible probe can readily be bent, folded, or rolled while being disposed at the internal treatment site. Thus, for example, a curved surgical needle (650) can be used to implant a flexible probe at the treatment site by drawing the flexible probe through tissue along a curved path to a desired position; one or more disk-shaped buttons (660, 670) that are attached to the ends of the flexible probe can be used to secure the flexible probe so that it does not move from the desired position.

RELATED APPLICATION

This application is a continuation-in-part application, based on priorcopending application Ser. No. 08/613,390, filed on Mar. 7, 1996, thebenefit of the filing date of which is hereby claimed under 35 U.S.C. §120.

FIELD OF THE INVENTION

This invention generally relates to a method for using a probe on whichis disposed an electronic device used to effect a medical procedure in apatient's body, and more specifically, to a probe adapted for insertioninto a patient's body through an incision or natural body opening, toimplement the medical procedure at a site within the patient's body.

BACKGROUND OF THE INVENTION

Abnormal cells in the body are known to selectively absorb certain dyesperfused into a treatment site to a much greater extent than surroundingtissue. For example, tumors of the pancreas and colon may absorb two tothree times the volume of certain dyes, compared to normal cells. Oncepre-sensitized by dye tagging, the cancerous or abnormal cells can bedestroyed by irradiation with light of an appropriate wavelength orwaveband corresponding to an absorbing wavelength or waveband of thedye, with minimal damage to normal tissue. This procedure, which isknown as photodynamic therapy (PDT), has been clinically used to treatmetastatic breast cancer, bladder cancer, lung carcinomas, esophagealcancer, basal cell carcinoma, malignant melanoma, ocular tumors, headand neck cancers, and other types of malignant tumors. Because PDT mayselectively destroy abnormal cells that have absorbed more of the dyethan normal cells, it can successfully be used to kill malignant tissuewith less effect on surrounding benign tissue than alternative treatmentprocedures.

Typically, invasive applications of PDT have been used during surgicalprocedures employed to gain access to a treatment site inside the bodyof the patient to administer light produced by relatively high intensitylight sources, such as high power lasers or solid state laser diode (LD)arrays. Optical fibers in a hand-held probe are often used to deliverthe intense light to the surgically exposed treatment site from a remotesource to reduce damage to surrounding tissue from the heat developed bythe light source.

It has been shown possible, in certain cases, to obtain improvedtherapeutic results in PDT at a low light level. As reported by J. A.Parrish in "Photobiologic Consideration in Photoradiation Therapy," pp.91-108, Porphyrin Photosensitization, Plenum Press, (1983), preliminarylaboratory studies with hematoporphyrin and visible light suggest thatlow intensity light may be more effective in PDT. In these experiments,subcutaneous tumors in the flanks of newborn rats were treated with thesame external dose of 620 nm radiation, at intensities of 7.5, 28, and75mW/cm². At the same total light dosage, Parrish found that greatertumor necrosis occurred at the lowest light intensity used.

Light emitting probes designed to be transcutaneously introduced intothe body of a patient at a desired treatment site, to administer PDTusing low light level sources, for extended periods of time, are taughtin commonly assigned U.S. Pat. No. 5,445,608, the drawings anddisclosure of which are specifically incorporated herein by reference.Several different embodiments of such probes are illustrated anddiscussed in this patent. Each of the probes disclosed in this referenceincludes a plurality of light sources that are mounted on a relativelystiff or inflexible substrate and enclosed within a transparent envelopethrough which light emitted by the light sources is transmitted to thetumor or other cells to be destroyed by the PDT. The light sources usedon the probes taught by this reference are preferably light emittingdiodes (LEDs). By transcutaneously inserting one of these probes into aninternal treatment site and applying PDT over an extended time frame,abnormal cells at the treatment site can be destroyed without adverseimpact on normal cells.

None of the implantable light emitting probes disclosed in theabove-referenced patent include light sources mounted on flexiblesubstrates. There are many applications for PDT in which it would beadvantageous to use a flexible substrate for mounting the LEDs or otherlight sources on a probe used to administer the PDT, e.g., so that theprobe can be threaded into a treatment site through a curved passagewithin the patient's body without risk of perforation of the passagewall. In contrast to the relatively inflexible substrate used in theprobes disclosed in the above-referenced patent, a flexible PDT probecould be folded or rolled into a smaller cross-sectional size forinsertion into a treatment site through an incision or body passage andthen allowed to deploy, unfolding or unrolling into a larger size foradministration of low intensity light to the treatment site.Alternatively, a flexible probe could be molded around an irregularlyshaped tumor or organ or rolled around a lumen, such as a blood vessel,or unfurled inside a passage or cavity of an organ or lumen to irradiateits interior with light emitted by the probe. In addition, a flexibleprobe would be able to change shape to adapt to changes in the treatmentsite, as malignant tissue is destroyed by the PDT, and should be able tomove with an organ (such as the lung or heart) or blood vessel, due to aphysiological displacement or change in the shape of the organ orvessel, without interfering with the function of the organ or vessel.The prior art does not disclose a flexible probe capable of providingthese capabilities.

It is also apparent that a flexible probe could more readily beintroduced to a treatment site for implementing medical procedures otherthan PDT. For example, a flexible probe that includes an ultrasonictransmitter and/or ultrasonic receiver could more readily be insertedinto an organ or lumen to carry out an ultrasound scan of surroundingtissue relative to the site inside the organ or lumen. Furthermore, aflexible probe that is used to administer PDT can be provided withelectronic components capable of carrying out additional functions. Forexample, a sensor to determine the efficacy of the PDT treatment mightbe included on a flexible probe, in addition to the plurality of LEDs orother light sources that are used to provide light to a treatment site.

A flexible probe on which an electronic circuit for administering amedical treatment or a sensing device is mounted can more readily bethreaded into an internal site than a rigid or inflexible probe, and theinsertion procedure can be implemented with less trauma to a patient. Inaddition, a flexible probe is less likely to cause an unwanted andpotentially harmful perforation, or to move from a treatment site withina patient's body. Thus, there are significant advantages to be realizedin using a flexible probe rather than a relatively rigid probe foradministering medical treatment or carrying out diagnostic procedures.By inserting a flexible probe into the patient's body through a smallincision and threading it to a site where it will be used in a medicalprocedure, the patient would likely be exposed to less risk of infectionand loss of blood than is occasioned by the more extensive surgery usedin conventional applications of the treatment. Further, a flexible probemay be left in place at a treatment site longer, due to the minimalimpact it has on the patient's normal physiological functions and due toits ability to adjust to changing conditions at the treatment site. Forthese and other reasons that will be evident from the followingdisclosure, a flexible probe offers substantial advantages over priorart approaches to administering PDT and other types of medical treatmentto an internal treatment site within a patient's body.

Because it can be readily deformed around a curved path, a flexibleprobe can more easily be conveyed to an internal treatment site than arigid probe. Endoscopic techniques can be applied for moving a flexibleprobe through a body passage and positioning it at or within a treatmentsite. It would be desirable to use a curved pointed object to draw aflexible probe along a curved path, defining a desired position for theflexible probe at a treatment site disposed within abnormal tissue. Oncepositioned at the treatment site, it will likely be necessary to affixthe probe, preventing its displacement away from the site due to naturalphysiological movement. Thus, some means would probably be required toensure that the flexible probe is secured in place.

SUMMARY OF THE INVENTION

The present invention is directed to a method for implanting and fixinga flexible probe in a desired position at a treatment site within apatient's body. The method uses a flexible probe that includes anelongate strip having sufficient flexibility to sustain deformation andbending without damage. The strip is attached to a surgical needle, andthe surgical needle is forced through tissue to the treatment sitewithin the patient's body. The strip comprising the flexible probe isdrawn into the tissue by the surgical needle, along a path of thesurgical needle. Once the strip is implanted with the surgical needle inthe desired position at the treatment site, the surgical needle isdisconnected from the strip. The surgical needle is then withdrawn fromthe tissue, leaving the strip disposed in the desired position withinthe patient's body to administer the medical treatment to the treatmentsite.

The method further includes the step of securing one end of the strip toa first object. The first object has a substantially greatercross-sectional size than the strip and serves to anchor the strip inthe desired position at the treatment site, preventing movement of thestrip relative to the treatment site. Optionally, the first object maybe secured to a tissue surface in the patient's body.

In addition, the method may include the step of securing another end ofthe strip to a second object. Like the first object, the second objecthas a substantially greater cross-sectional size than the strip andfurther serves to anchor the strip in the desired position at thetreatment site, preventing movement of the strip relative to thetreatment site. The second object preferably includes a sleeve thatslips over the strip. A lead that is coupled to the strip extendsthrough the sleeve. The method further preferably includes the step ofsecuring the second object to the strip after the strip is disposed atthe desired position. The step of securing the first and/or the secondobject to the strip may be accomplished either by crimping the sleeve ofthe object about the strip, by affixing the object with a threadedfastener (e.g., a set screw disposed in the sleeve), by inserting a pinthrough the sleeve and the strip, or by adhesively connecting the objectto the strip, or by affixing the object to the strip in some othermanner, such as with a suture.

In addition, the step of forcing the surgical needle may be accomplishedby grasping the surgical needle with a needle holder, and/or pulling thesurgical needle into the desired position with forceps.

Another aspect of the present invention is directed to apparatus foradministering a medical procedure to a treatment site disposed within apatient's body. Elements of the apparatus are generally consistent withthose noted in the above description of the method, and the componentsof the apparatus perform substantially the functions implemented in thesteps of the method described above.

BRIEF DESCRIPTION OF THE DRAWING FIGURES

The foregoing aspects and many of the attendant advantages of thisinvention will become more readily appreciated as the same becomesbetter understood by reference to the following detailed description,when taken in conjunction with the accompanying drawings, wherein:

FIG. 1 is a greatly enlarged side view of a distal portion of a firstembodiment of a flexible probe in accord with the present invention;

FIG. 2 shows cross-sectional views of four different profiles of theflexible probe;

FIG. 3 is a greatly enlarged side view of a distal portion of a secondembodiment of the flexible probe;

FIG. 4 is side elevational view of a straight guide tube through whichthe flexible probe is delivered to an internal treatment site, showingthe flexible probe being guided through a lumen of the guide tube;

FIG. 5 is a side elevational view of a curved guide tube through whichthe flexible probe is delivered to an internal treatment site, showingthe flexible probe being guided through a lumen of the guide tube;

FIG. 6A is a side view of the straight guide tube of FIG. 4, showing theguide tube used to deliver the second embodiment of the flexible probeto a treatment site inside a tumor or other type of tissue mass;

FIG. 6B is a side view of the straight guide tube, showing it beingdrawn back from the treatment site over an electrical lead that iscoupled to the second embodiment of the flexible probe;

FIG. 7 is a side view showing the flexible probe sutured to a tissuelayer to secure the flexible probe in a treatment site;

FIG. 8 is an isometric view of a prior art peel-away sheath;

FIG. 9 is a plan view of the prior art peel-away sheath of FIG. 8;

FIG. 10 is a side view of the prior art peel-away sheath of FIG. 8 and aprior art lancet that is used to position the peel-away sheath in atissue mass;

FIG. 11 is a side view showing the prior art lancet being withdrawn fromthe peel-away sheath of FIG. 8;

FIG. 12 is a side view showing the flexible probe being positioned inthe tissue mass through the peel-away sheath of FIG. 8;

FIG. 13 is a side view illustrating how the peel-away sheath is removedfrom the second embodiment of the flexible probe by splitting the guidetube longitudinally while withdrawing it from the tissue mass;

FIG. 14 is an isometric cut-away view of a third embodiment of thepresent invention and a catheter for inserting a plurality of flexibleprobes through a body passage to a treatment site within a patient'sbody;

FIG. 15 is a sectional view of a penis, showing the third embodiment ina catheter that is inserted into a bladder through a urethra passage;

FIG. 16A is a sectional view of the bladder, showing the catheter beingwithdrawn and the plurality of flexible probes splaying apart inside thebladder;

FIG. 16B is a side view of a portion of a fourth embodiment of aflexible probe formed as a loop, shown in a flattened or compressedstate;

FIG. 16C is a side view of the fourth embodiment of the flexible probein an open, uncompressed state;

FIG. 16D is a sectional view of the bladder in which a plurality ofprobes in accord with the fourth embodiment are shown in a splayed arrayas the catheter used to introduce the probes into the bladder iswithdrawn;

FIG. 17 is an isometric view of a fourth embodiment of the flexibleprobe configured as a flexible sheet;

FIG. 18 is an isometric view of the fourth embodiment of the flexibleprobe folded to reduce its transverse size and tied with a suture torestrain it in the folded configuration;

FIG. 19 is an isometric view of the fourth embodiment of the flexibleprobe folded to reduce its transverse size and clipped with a U-shapedclip to restrain it in the folded configuration;

FIG. 20 is an isometric view of the fourth embodiment of the flexibleprobe folded to reduce its transverse size and clipped with arectangular-shaped band to restrain it in the folded configuration;

FIG. 21 is a sectional view of the fourth embodiment of the flexibleprobe, showing the flexible probe being pulled by forceps from oppositeends to unfold it at a treatment site in a body lumen;

FIG. 22 is a side view of the fourth embodiment of the flexible probe,showing the sheet rolled into a cylindrical configuration;

FIG. 23 is an end view of the rolled flexible probe of FIG. 22;

FIG. 24 is an end view of the rolled flexible probe of FIG. 22,restrained in a cylindrical sleeve;

FIG. 25 is an elevational view of the rolled flexible probe of FIG. 24;

FIG. 26 is a sectional view of a portion of a patient's torso, showingthe rolled fourth embodiment being positioned at a treatment sitethrough an access tube that extends through the cutaneous layer;

FIG. 27 is a sectional view of the portion of the torso, showing therestraining sleeve being removed from the rolled flexible probe;

FIG. 28 is a sectional view of a treatment site inside a patient's body,showing the flexible probe being unrolled at the treatment site;

FIG. 29 is a sectional view of an internal passage in a patient's bodyin which the rolled flexible probe has been inserted;

FIG. 30 is the sectional view of the internal passage showing theflexible probe held in position by sutures that connect loops on theflexible substrate to interior surfaces of the passage;

FIG. 30A is an isometric view of the rolled flexible probe, restrainedby a suture that holds opposite ends of the rolled configuration inplace;

FIG. 31 is an isometric view of the fourth embodiment of the flexibleprobe rolled around a body lumen having a first cross-sectional size;FIG. 32 is an isometric view of the fourth embodiment of the flexibleprobe rolled around a body lumen having a second cross-sectional size,showing how the rolled diameter of the flexible probe increases toaccommodate physiological changes at a treatment site;

FIG. 33 is a sectional view of a patient's organ showing a fifthembodiment of the flexible probe that includes a balloon cuff, withlumens and leads extending through an opening in the patient's skin;

FIG. 34 is an isometric view of the fifth embodiment of the flexibleprobe;

FIG. 35 is a side view of the fifth embodiment of the flexible probe;

FIG. 36 is a sectional view showing a flexible probe threaded through anasal passage and into the entrance of a patient's stomach;

FIG. 37 is sectional view of a portion of the esophagus in which theflexible probe has been threaded;

FIG. 38 is a sectional view showing a flexible probe having electricallines attached to one end and a suspension lead attached to the otherend and extending through the esophagus and out through the nasalpassage of a patient;

FIG. 39 is a sectional view of a portion of the esophagus in which theflexible probe of FIG. 38 is disposed;

FIG. 40 is a side view of a sixth embodiment of the flexible probe inwhich a soft tip is temporarily attached to a distal end of the probe sothat peristalsis advances the probe into the bowel;

FIG. 41 is a sectional view of the bowel, showing the flexible probesutured in place and a proximal end of an attached lead passing througha gastrostomy site in the stomach and out through the abdominal wall;

FIG. 42 is a sectional view of a bowel, showing the flexible probesutured at a treatment site inside the bowel and leads extending outsidethe abdominal cavity through a stoma site;

FIG. 43 is a side view of a branching artery, showing a seventhembodiment of the flexible probe coiled about the artery;

FIG. 44 is an isometric view of a heart showing the fourth embodiment ofthe flexible probe overlying a cardiac vessel;

FIG. 45 is a sectional view of a cardiac vessel showing arteriosclerosisplaque built up on the interior surface;

FIG. 46 is a plan view of a flexible substrate upon which a plurality ofLEDs can be mounted to produce a plurality of flexible probe circuits;

FIG. 47 is a plan view of a single flexible substrate probe substrateand conductive strips for mounting a plurality of LEDs;

FIG. 48 is an enlarged side view of a distal end of a flexible probe inwhich a plurality of LEDs are mounted on opposite sides of flexiblesubstrates;

FIG. 49 is a cross-sectional view of the flexible probe shown in FIG.48;

FIG. 50 is a block diagram of a system for administering PDT using theflexible probe;

FIG. 51 is a plan view of the PDT flexible probe;

FIG. 52 is a block diagram showing the components of a PDT system thatuses a flexible probe;

FIG. 53 is a greatly enlarged cut-away view of an embodiment of aflexible probe in which light sources are mounted between two facingflexible substrates;

FIG. 54 is a cross-sectional view of the embodiment shown in FIG. 53;

FIG. 55 is a plan view of another embodiment of a flexible probe formedas a sheet, for administering PDT;

FIG. 56 is a cross-sectional view of the embodiment of FIG. 55, takenalong section lines 56-56;

FIG. 57 is an isometric view of a portion of an embodiment in which LEDshaving two characteristic wavebands are mounted between conductivetraces on a flexible substrate, with the polarities of the LEDs havingone characteristic waveband reversed relative to those having the othercharacteristic waveband;

FIG. 58 is a cross-sectional elevational view of the embodiment of theflexible probe shown in FIG. 57;

FIG. 59 is a plan view of a planar array of LEDs mounted on a flexiblesubstrate that is encapsulated in a transparent material;

FIG. 60 is a sectional view of a pair of conductive traces on which anLED is mounted on a reflector;

FIG. 61 is an isometric view of power transmitter and receiver coilsdisposed on opposite sides of a cutaneous layer;

FIG. 62 is an alternative embodiment of power transmitter and receivercoils disposed on opposite sides of a cutaneous layer; FIG. 63illustrates an infrared source and receiver disposed on opposite side ofa cutaneous layer, for transmitting power for the flexible probe;

FIG. 64 is an exploded isometric view showing a distal end of theflexible probe and an object that is affixed to the flexible probe;

FIG. 65 is a sectional view showing a path described by a curvedsurgical needle that is used to implant a flexible probe at a treatmentsite;

FIG. 66 is a sectional view showing the flexible probe of FIG. 65secured at the treatment site by an object attached to the flexibleprobe; and

FIG. 67 is a sectional view showing the flexible probe of FIG. 66 with asecond object attached to the other end of the flexible probe to secureit at the treatment site.

DESCRIPTION OF THE PREFERRED EMBODIMENT

Elongate Flexible Probes

A first embodiment of a flexible probe 100 in accordance with thepresent invention is illustrated in FIG. 1. Flexible probe 100 iselongate in shape and comprises a flexible substrate 102 comprising apolymer material that readily bends without breakage. In an initialprototype of the flexible probe, the polymer material used isapproximately 0.002" thick and comprises Kapton™ polyimide film, whichis sold by E. I. DuPont De Nemours & Co. Other types of polymers andthinner material can be used for the flexible substrate in each of theembodiments of the present invention that are described below. Theflexible substrate comprising flexible probe 100 (and the otherembodiments described below) is sufficiently flexible and strong toenable it to be folded back on itself (through an angle of about 180°)along a line, rolled, twisted, and otherwise distorted, without anydamage to the substrate or to conductive traces (discussed below inregard to FIG. 46) that are applied to the flexible substrate.

Although not shown in FIG. 1, a plurality of conductive traces areapplied to flexible substrate 102 to convey an electrical current toenergize a plurality of light emitting sources 104 that are mounted onand supported by the flexible substrate. In connection with thisinvention, it is also contemplated that other types of electronicmicrocircuits may be mounted on the flexible substrate instead of, or inaddition to, light emitting sources 104. Such electronic microcircuitsmay include ultrasonic transmitters and emitters, sensors such asphotodetectors, and other electronic circuitry for use in effectingeither a medical treatment or a diagnostic function using the flexibleprobe within a patient's body. It should be noted that the presentinvention is not limited for use with human patients, but may also beused, for example, by veterinarians to treat and/or diagnose medicalproblems in pets, livestock and other animals. For use in administeringlight during PDT, flexible substrate 102 and light emitting sources 104are enclosed in a clear (light transparent) biocompatible polymerenvelope 106. In this and other of the embodiments intended for use inproviding PDT, the light emitting sources preferably comprise LEDs;however, it is also contemplated that other types of light emittingelectronic circuits, such as laser diodes or a thin filmelectroluminescent panel can alternatively be fabricated on the flexiblesubstrate for use in administering the PDT. For example, thin filmelectroluminescent display panels using ZnS:Mn phosphors are well knownin the prior art and the flexible substrate is equally applicable as asupport for a plurality of conductive traces, between which aresandwiched the light-emitting phosphor layers.

FIG. 2 illustrates various other cross-sectional shapes for the envelopeprovided for the flexible probe. These shapes include an envelope 106'that has a rectangular cross section and encloses a flexible substrate102', which is sufficiently broad to enable a plurality of lightemitting sources 104 to be mounted across its width. Also illustratedare an envelope 106", which has a generally half-round cross-sectionalshape, and an envelope 106"' an equilateral triangle cross-sectionalshape. The various cross-sectional shapes illustrated for the envelopein FIG. 2 are merely exemplary of various cross-sectional shapescontemplated for use with flexible probes made in accordance with thepresent invention.

No attempt is made in this disclosure to teach optimum exposure timesand light intensities for conducting PDT using the present invention.Planned clinical trials will help to determine such variables forvarious types of abnormal tissue and in regard to patient specificvariables. The basis premises of PDT are well known to those of ordinaryskill in this art and need not be recited to fully disclose the presentinvention. For example, a variety of photoreactive agents are known, asevident from references such as "Photosensitizing Activity of Water andLipid-Soluble Phthalocyanines on Escherichia coli," Bertoloni et al.,"Photodynamic Effects of Dyes on Bacteria," Webb et al., "Phototoxicityof Quinilone Methanols and Other Drugs," Ison et al., "Research Progressin Organic-Biological and Medicinal Chemistry," Ballio et al.,"Photodynamic Therapy with Endogenous Protoporphyrin," Kennedy et al.,and "Immunophototherapy for the Treatment of Cancer of the Larynx,"Schlager et al. It is contemplated that conventional photoreactiveagents of the types discussed in the preceding references can be veryeffective in implementing PDT using the present invention. Eventually,it is likely that even more effective photoreactive agents will beidentified for use in extended term PDT, which the present invention iswell suited to provide.

In FIG. 3, a second embodiment of a flexible probe 108 is illustrated.Flexible probe 108 differs from the first embodiment by including aflexible envelope 110 on which is formed a loop 112. Loop 112 includesan orifice 114, which as shown below, provides an attachment point fortemporarily mounting flexible probe 108 in a fixed position at atreatment site inside a patient's body. Flexible probe 108 also includesa barb 116 disposed at its distal end. Barb 116 is formed of the polymermaterial comprising envelope 110 and has a characteristic elasticitythat causes the barb to flex to an open position in which it extendsoutwardly from the longitudinal axis of the flexible probe, as shown inFIG. 3. However, because it is flexible, barb 116 can readily be closedto minimize the cross-sectional area of flexible probe 108 at its distalend.

As explained below, flexible probes made in accordance with the presentinvention can be placed at a treatment site within a patient's body inways that benefit from the flexibility of the flexible probe and itsability to bend or fold. In FIG. 4, a guide tube 120 is illustratedhaving a pointed end 122 for piercing a cutaneous layer (or other tissuelayer) of a patient's body (not shown) or for piercing the outer surfaceof an internal organ in which is disposed a treatment site to which theflexible probe is to be advanced and left in place. In FIG. 5, a guidetube 120' is illustrated that has a predefined radius of curvature and adistal end terminating in a sharp point 122' for piercing the cutaneouslayer or outer surface of an organ to facilitate placement of flexibleprobe 108. Due to the characteristic flexibility of flexible probe 108,it is easily advanced around the radius of curvature of guide tube 120'for insertion and disposition at the treatment site within the patient'sbody. Electrical power and/or signals to and from the circuitrycomprising the flexible probe are conveyed through leads 118, whichextend either outside the patient's body or to a site remote from thetreatment site where power and/or signals pass through the cutaneouslayer of the patient's body. Details of such an arrangement arediscussed below.

FIGS. 6A and 6B illustrate the steps involved in disposing flexibleprobe 108 at a treatment site within a tumor 124. Sharpened end 122 ofguide tube 120 is inserted into tumor 124 to an appropriate depth, e.g.,just past the center of the tumor. Flexible probe 108 is eithercontained within guide tube 120 during its insertion, or is subsequentlyinserted into the tumor through the inner passage of guide tube 120after the guide tube has been positioned within tumor 124. Thereafter,guide tube 120 is withdrawn over the leads extending to flexible probe108, as the flexible probe is held in place. Barb 116 flexes outwardlyas the distal end of the flexible probe extends from the distal end ofthe guide tube. The barb engages tissue inside tumor 124, preventingflexible probe 108 being pulled from inside tumor 124 as the guide tubeis withdrawn. Optionally, a suture 126 may be used to secure loop 112 onflexible probe 108 to tumor 124 (or to another adjacent soft tissuestructure). Guide tube 120 is withdrawn from the patient's body, andleads 118 are coupled to a power source and/or other instrumentation toactivate the electronic circuits on the flexible probe.

An alternative embodiment of a flexible probe 130 is shown in FIG. 7,following its insertion into tumor 124. Flexible probe 130 includes twoloops 112 that extend outwardly from opposite sides of the flexibleenvelope. As shown in FIG. 7, loops 112 are secured by sutures 131 toadjacent tissue 128 to retain flexible probe 130 fixed within tumor 124.

Another technique for inserting a flexible probe into tumor 124 (or intoanother type of tissue mass) employs a peel-away sheath 132, which iswell known to those of ordinary skill in the art. Peel-away sheath 132is shown in FIGS. 8-13, which illustrate its configuration and its usein placing flexible probe 108 at a treatment site within tumor 124. Asshown in FIG. 9, peel-away sheath 132 is shaped as an annular cylinderhaving frangible seams 134 disposed on opposite sides of the cylindricalsheath, extending longitudinally along its length. A lancet 138 having asharpened point 122 is inserted inside a bore 136 of peel-away sheath132, so that the sharpened point extends beyond the distal end of thesheath, and the assembly is inserted within tumor 124, as shown in FIG.10. Sharpened end 122 enables the assembly to readily pierce through acutaneous layer or other tissue surface and enables the assembly to bereadily advanced into tumor 124 (or into other types of tissue mass).

In FIG. 11, lancet 138 is withdrawn from peel-away sheath 132, whichremains temporarily fixed within a passage 140 in the tumor, produced byinsertion of the assembly. Then, as shown in FIG. 12, flexible probe 108is inserted through the bore of peel-away sheath 132 and into passage140 so that the flexible probe extends beyond the distal end of thepeel-away sheath and inside tumor 124. The flexibility of the flexibleprobe facilitates threading it to the point in the patient's body whereit can be inserted in the bore of the sheath. To reach this point, itmay be necessary to pass the flexible probe through a body lumen oralong a curved path within the body. Finally, as shown in FIG. 13, sides132a and 132b of the peel-away sheath are split apart from each otheralong frangible seams 134 using forceps (endoscopic or conventional)142. The forceps simultaneously split the frangible seam and withdrawsides 132a and 132b from inside tumor 124. Flexible probe 108 is held inplace within tumor 124 by barb 116, which engages tissue in the interiorof the tumor.

Since a flexible probe made in accordance with the present invention canreadily bend, it is easily threaded into a treatment site within apatient's body, through an internal body or organ lumen. An example inwhich the present invention is used to apply PDT inside a male patient'sbladder is illustrated in FIGS. 14-16 (A-D). In FIG. 14, a urinarycatheter 150 is illustrated that includes a central lumen 152. Withincentral lumen 152 is disposed a guide lumen 154, which exits urinarycatheter 150 adjacent a proximal end of the urinary catheter. Guidelumen 154 guides a bundle 156 of flexible probes 158 that are insertedinto the guide lumen from its proximal end and extend just past thedistal end of urinary catheter 150. Also disposed within lumen 152 is aballoon inflation lumen 160, having a distal end in fluid communicationwith a balloon 170 that is disposed at the distal end of urinarycatheter 150. Inflation lumen 160 is also in fluid communication with anexternal line 162, to which it is attached adjacent the proximal end ofthe urinary catheter. External line 162 terminates in a connector 164that is suitable for connecting to a source of compressed air (or othertype of fluid under pressure) used to inflate balloon 170. Balloon 170extends annularly around the outer perimeter of the distal end ofurinary catheter 150, but is not inflated until after the distal end ofthe urinary catheter and balloon 170 have been inserted into thepatient's bladder. Extending from the distal ends of each of theflexible probes 158 comprising bundle 156 are electrical lines 166,which are combined in leads 168. Leads 168 are connected to a source ofelectrical current and to instrumentation appropriate to process signalsconveyed from the flexible probes.

A portion of lumen 152 remains open along the entire length of urinarycatheter 150, enabling urine to pass freely through lumen 152 to anexternal receptacle (not shown). As illustrated in FIG. 15, urinarycatheter 150 is threaded through a urethra 172, past a pubic bone 180,seminal glands 178, and prostate gland 176 into a patient's bladder 174.Balloon 170 is then inflated with pressurized air or other pressurizedfluid and the urinary catheter is drawn back through urethra 172 so thatballoon 170 seats within the opening into bladder 174, forming a sealingcuff. As urinary catheter 150 is drawn backwards along bundle 156,flexible probes 158 splay outwardly apart from each other, within theinterior of bladder 174. Although not shown in FIG. 16A, light sourceswithin each of flexible probes 158 are energized to provide PDT therapyto the interior surface of bladder 174 for treatment of tumors and othermedical disorders that are appropriately treated using PDT.

FIGS. 16B-16D illustrate a flexible probe 182 in which the distal end ofthe flexible probe is turned back toward itself in a loop and adhesivelyattached at a point 186, as shown in FIG. 16C. The loop is sufficientlyflexible to be collapsed, but its inherent elasticity causes it tospring into an open loop when not restrained. Inside flexible probe 182is provided a flexible substrate 184 on which a plurality of lightsources (not visible in the drawing figures) are mounted. As illustratedin FIG. 16B, use of flexible probes 182 in urinary catheter 150 toprovide PDT inside a hollow organ, such as bladder 174, increases thetotal area of the flexible probe from which light is emitted anddecreases any risk of perforating the organ wall with the tip of theflexible probe. When urinary catheter 150 is withdrawn from the bundleof flexible probes 182, the probes not only splay outwardly from eachother, but also each form an open loop to increase the total area fromwhich light is emitted from the flexible probes.

Flexible Sheet Probes

In FIGS. 17-21, use of a flexible sheet probe 190 is illustrated inaccordance with the present invention. Flexible sheet probe 190 includesa generally quadrilateral shaped flexible substrate 196. This embodimentcomprises a flexible substrate sheet that is substantially wider andlonger than it is thick. It is contemplated that the flexible sheetprobe can be made in any of a variety of different shapes, such as"T-shaped," "L-shaped," round, oval, etc., as is appropriate for aparticular application. A plurality of light sources (or othermicro-electronic circuits) 192 are mounted on opposite surfaces offlexible substrate 196. Electrical power and/or signals are conveyed toeach of light sources 192 (or other microcircuits) over leads 194, whichare coupled to electrical traces disposed internally (not shown) betweenopposite outwardly facing surfaces of substrate 196.

FIG. 18 illustrates how flexible sheet probe 190 is folded transverselyinto three layers to reduce the cross-sectional width of the resultingpackage, thereby permitting the flexible sheet probe to be more readilyinserted into a treatment site through an access incision or internalbody passage having a limited transverse dimension, e.g., through anincision less than two cm. in length. After the flexible sheet probe isfolded in a tri-fold configuration 198 as shown in FIG. 18, a suture 200is used to restrain it, preventing flexible sheet probe 190 fromprematurely unfolding prior to its placement at a treatment site.

FIGS. 19 and 20 illustrate how a flexible sheet probe 196' that isformed of a elongate quadrilateral-shaped flexible substrate is foldedlengthwise into three layers and restrained for insertion to a treatmentsite within a patient's body. In FIG. 19, a hairpin-shaped clip 204 isinserted over folded flexible sheet probe 196' to restrain it in atri-fold configuration 198'. Similarly, in the embodiment shown in FIG.20, a rectangular clip 206 having an internal opening sized to fit overtri-fold configuration 198' retains the folded state until the foldedflexible sheet probe has been inserted into the treatment site.

FIG. 21 illustrates how, having removed the restraint (i.e.,hairpin-shaped clip 204 or rectangular clip 206), the flexible sheetprobe is unfolded within a space 214 that is disposed between layers oftissue 210, to apply PDT or other medical treatment or diagnosticprocedure to an adjacent tumor or lesion 212. As indicated in FIG. 21,forceps 216 are used to grip opposite ends of flexible sheet probe 196',thereby enabling it to be unfolded so that it overlies tumor or lesion212.

Disposition of Flexible Probes at Various Treatment Sites

In FIGS. 22-28, use of a flexible sheet probe 220 is illustrated.

Flexible sheet probe 220 comprises a flexible substrate 222, whichincludes light sources and/or other micro-electronic circuitry mountedthereon in contact with conductive traces (none of which are shown). Theflexibility of flexible sheet probe 220 facilitates its insertion in atreatment site inside a patient's body using a laparoscopic procedure.Flexible sheet probe 220 is preferably rolled into concentriccylindrical layers around a cylinder template 228. The roll of flexiblesubstrate 222 is then restrained inside a sleeve 226, generally as shownin FIGS. 22-25.

A push rod 240 is used to insert the rolled flexible sheet proberetained by sleeve 226 through a guide tube 238. The guide tube issurgically positioned so that it extends through a cutaneous or othertissue layer 232 to access an internal treatment site 230. In addition,an instrument guide 234 and a laparoscopic tube 236 are inserted throughcutaneous or other tissue layer 232 from opposite sides of guide tube238 so that their distal ends are disposed adjacent treatment 230.Flexible sheet probe 220 will be deployed and unrolled to administer PDTor other medical therapy at treatment site 230.

In FIG. 27, laparoscopes 241 are inserted through laparoscope tube 236and guide tube 234. Forceps 244 are then used to grasp cylinder template228 and sleeve 226 to enable the sleeve to be withdrawn from rolledflexible substrate 222. Push rod 240 is also withdrawn through guidetube 238. Eye pieces 242, which are provided on each of the twolaparoscopes 241, enable the operator to manipulate rolled flexiblesubstrate 222 and sleeve 226 during this procedure. Next, as shown inFIG. 28, forceps 246 are inserted through guide tube 238 to grasp sleeve226, withdrawing it from treatment site 230. In addition, laparoscopes241 are used to unroll flexible substrate 222 at treatment site 230,thereby preparing it to administer PDT or other medical therapy.Although this step is not shown, forceps 246 are also used to withdrawtemplate 228 through guide tube 238.

A cylindrical configuration for a flexible sheet probe 250 is shown inFIGS. 29-32. This embodiment comprises a flexible substrate 252 that isloosely rolled into a cylinder defining a passage 248 in the center ofthe cylinder through which fluids can readily flow when the flexiblesheet probe is disposed within a body lumen. Disposed on an outersurface of flexible sheet probe 250 are a plurality of light sources256, which are arranged in a closely spaced-apart array so that lightemitted thereby irradiates the surface of a tumor (or other abnormaltissue) 258. Tumor 258 is disposed on the interior of a lumen 260. Lumen260 may, for example, comprise a patient's esophagus or a blood vessel.A lead 254 conveys electrical current from a remote site, to energizethe light sources and may optionally include additional conductors forconveying other signals to or from other types of micro-electroniccircuitry mounted on flexible substrate 252.

In FIG. 30, a flexible sheet probe 250' is illustrated that includes twoloops 262 along one edge. Sutures 264 are passed through the loops in alaparoscopic or endoscopic procedure, to secure the flexible sheet probefixed adjacent tumor 258 on the interior of lumen 260. Optionally, arestraint line 266 may be attached to the opposite end of flexible sheetprobe 250', further securing the flexible sheet probe fixed at thetreatment site within passage 260.

One of the advantages of flexible sheet probes 250 and 250' is theircharacteristic elasticity that causes them to expand outwardly to alarger diameter as tumor 258 shrinks in response to the PDT or othertherapy provided by the flexible sheet probe. Consequently, the lightsources (or other micro-electronic circuits) mounted on flexiblesubstrate 252 continue to remain in close proximity to the surface ofthe tumor as it contracts in response to the therapy.

In FIG. 30A, a further alternative flexible sheet probe 250" isillustrated. This embodiment includes loops 268 formed on flexiblesubstrate 252, so that the loops are disposed proximate to each otherwhen the flexible substrate is elastically formed into a cylinder. Asuture 270 connects loops 268 to restrain the flexible substrate in therelatively small diameter, cylindrical configuration for placement at aninternal treatment site. Suture 270 is then cut, enabling thecharacteristic elasticity of flexible substrate 252 to increase thediameter of the cylindrical shape so that it conforms to the internaldiameter at the treatment site.

In FIGS. 31 and 32, a flexible sheet probe 250"' is illustrated having aplurality of light sources (not shown) on its inner surface. Thisembodiment is intended for use in treating the external surface of ablood vessel 272 (or other organ lumen) about which cylindrical form250"' is placed. Again, a restraint line 266 is optionally provided tohold the flexible probe in position at the treatment site, in oppositionto an opposing force applied through lead 254. As shown in FIG. 32,flexible sheet probe 250"' is formed into a tight cylindrical shape,which is the relaxed configuration of the flexible substrate. Because ofthe characteristic elasticity of the flexible substrate, the flexiblesheet probe readily changes diameter to compensate for changes in thediameter of blood vessel 272 or other organ lumen about which itscylindrical shape is disposed. For example, as shown in FIG. 32, bloodvessel 272 has a larger diameter than it does in FIG. 31, so that theoverlap of opposite ends of flexible substrate 252 is less in FIG. 32for the larger diameter blood vessel than it is in FIG. 31 for thesmaller diameter blood vessel. As a result, the light sources or otherelectronic circuits mounted on the inner surface of the flexible sheetprobe remain in intimate contact with the outer surface of the bloodvessel as its diameter changes.

Turning now to FIG. 33, yet a further flexible sheet probe 280 having anormal cylindrical shape is illustrated for use in applying PDT to atumor or lesion 278 disposed on the inner surface of an esophagus 292,at a point immediately adjacent to a stomach 294. Fluids flowing throughesophagus 292 readily pass through the center of flexible sheet probe280 and into stomach 294. A plurality of light sources 286 are disposedin spaced-apart array on a flexible substrate 282 that comprisesflexible sheet probe 280. An upper end of flexible substrate 282includes a balloon cuff 284, which is used to secure flexible sheetprobe 280 in place, to administer PDT to the tumor.

An opening in a wall 296 of stomach 294 is aligned with a correspondingopening through a cutaneous layer 298 for insertion of a gastrostomytube 300. A restraint balloon 310, which is disposed at the inner end ofthe gastrostomy tube, holds it in place and retains wall 296 of thestomach in position against the inner surface of cutaneous layer 298.

Passing through gastrostomy tube 300 are fluid lines 302, 304, and 306.Fluid line 302 is used to supply compressed air to inflate restraintballoon 310. Fluid line 304 is coupled in fluid communication withballoon cuff 284 through a fluid line 290 that extends from the ballooncuff through stomach 294. The balloon cuff is inflated using compressedair conveyed through fluid lines 290 and 304. Fluid line 306 connects toan internal fluid line 308 within stomach 294 that is used foraspirating fluid from the stomach or for adding medicaments. Inaddition, a lead 288 conveys electrical power to flexible sheet probe280 to energize light sources 286 and can also be used for conveyingsignals to and from other micro-electronic circuitry mounted on flexiblesubstrate 282. A flexible sheet probe 280' is illustrated with ballooncuff 284 inflated in FIG. 34, and with the balloon cuff deflated, inFIG. 35.

FIGS. 36 and 37 illustrate an alternate approach for positioningflexible probe 100 at a gastroesophageal junction 318 to provide PDT toa tumor 320 that is disposed at that point. In this approach, flexibleprobe 100 is inserted through the nasal passage of a patient 314,threaded through the patient's esophagus 292, and positioned so that thelight emitting sources 102 are disposed adjacent tumor 320.

Yet a further alternative embodiment for positioning a flexible probe100' adjacent tumor 320 is illustrated in FIGS. 38 and 39. Flexibleprobe 100' includes a restraint line 322 that extends through a nasalpassage 324, while a lead 316 extends from the interior of the patient'sstomach through gastrostomy tube 300 to an external power supply 326.Restraint line 322 is encapsulated within the clear biocompatible sheath106 of flexible probe 100'.

It may be desirable to treat tumors and lesions that are disposed insideeither the small or large intestine of a patient. In FIG. 40, anelastomeric bullet 330 is affixed to the distal end of flexible probe100 using either a suture 332 or an elastic band that compresses theelastomeric bullet about the outer diameter of the flexible probe.Elastomeric bullet 330 has a substantially larger cross-sectional areathan that of flexible probe 100, so that the natural peristalsisoccurring within the small and large intestine advances the flexibleprobe from the stomach to a desired treatment site in the bowel. Oncethe flexible probe reaches the treatment site, suture or elastic band332 is cut using an endoscopic procedure, and the elastomeric bullet iscarried through the intestine and exits the patient's body during anormal bowel movement or is extracted endoscopically.

With reference to FIG. 41, a lead 316 connected to flexible probe 100extends from the treatment site through the patient's large bowel 346and small bowel 344, exiting stomach 294 through gastrostomy tube 300.To ensure that flexible probe 100 remains fixed at the treatment sitewhere a tumor or lesion 352 is disposed on the internal surface of largebowel 346, loops 348 are attached with sutures 350 to the tissue of thebowel. An endoscope or colonscope is employed to place the sutures.

A disadvantage of the approach illustrated in FIG. 41 is the relativelylong length required for lead 316, which must extend from the treatmentsite disposed near the lower end of large bowel 346 into stomach 294.The total length of lead 316 may easily exceed 25-30 feet. In FIG. 42,an alternative approach is shown, which employs a Bishop-Koop procedureto create an enterocutaneous fistula by transecting large bowel 346 at apoint immediately above and adjacent to tumor 352. Sutures 356 areplaced to connect the lower portion of the bowel to a new opening 354made in the wall of the upper portion of the large bowel, adjacent thetransection in the upper portion of the large bowel. A transected end358 of the upper portion of the large bowel is then attached by sutures360 to an opening 362 in abdominal wall 340, thereby enabling arelatively short lead 316 to exit the patient's body. Waste matterpassing through large bowel 346 will continue to be moved through bothsections of the transected bowel by peristalsis.

A flexible probe 370 having loops 376 disposed at each end is shown inFIG. 43. This embodiment illustrates an application in which theflexible probe is helically coiled around an artery 380 and secured ateach end with sutures 378 that fasten loops 376 to adjacent tissue. Alead 372 extends from one end of the flexible probe to a power supply374. Flexible probe 370 can thus be used, for example, in applying PDTto treat arteriosclerotic deposits inside artery 380 within the regionabout which the flexible probe is coiled. Light emitted by the lightsources in the flexible probe is transmitted through the wall of theartery and absorbed by photoreactive dye-perfused arterioscleroticdeposits, causing the deposits to breakdown.

A flexible sheet probe 390 is shown in FIG. 44 for use in effecting PDTtreatment of a congested coronary artery 398. The four corners offlexible sheet probe 390 are sutured to the pericardium lining around aheart 396 so that a flexible substrate 392 is disposed inside thepericardium lining. Since the pericardium lining is opaque and does notreadily transmit light, the pericardium lining must be incised so thatthe flexible sheet probe can be disposed adjacent the coronary arterybeing treated and molded around the curved surface of the heart. Lightemitted by the light sources mounted on the flexible probe thus passesinto the interior of the coronary artery. A lead 394 extends fromflexible substrate 392 to a remote power source that supplies electricalcurrent to energize the light sources. FIG. 45 illustratesarteriosclerotic deposits 402 in a blood vessel or coronary artery thatmay be treated using PDT administered with the present invention.

FIGS. 64 through 66 illustrate a method and apparatus for implanting andfixing flexible probe 100 within a tumor 654 (or other abnormal tissue)comprising a treatment site within a patient's body. Although flexibleprobe 100 is illustrated in these Figures as an example of one type offlexible probe useful in effecting this aspect of the invention, it willbe apparent that other types of flexible probes that include a strip offlexible substrate that is relatively long compared to its transversedimension can be used instead.

As shown in FIG. 65, a curved surgical needle 650 is forced throughnormal tissue 656 and along a curved path through tumor 654. This curvedpath defines a desired position for a flexible probe to be disposed toadminister PDT or some other medical procedure or therapy. In thedisclosed example, flexible probe 100 is connected to curved surgicalneedle 652 and drawn along after the needle along the curved pathdefined by the passage of curved surgical needle's sharp point throughnormal tissue 656 and tumor 654. Although not illustrated in the Figure,a straight surgical needle can alternatively be used. At a point wherethe distal end of the flexible probe exits through a surface of tissue(possibly inside the patient's body), curved surgical needle 650 isdetached from flexible probe 100 and withdrawn. Since this procedure maybe accomplished endoscopically, the curved surgical needle may bewithdrawn either through a natural body opening or through an incision.It is also contemplated that the distal end of flexible probe may exitthe patient's body through a cutaneous layer. In either case, the mainbody of the flexible probe is thus disposed in a desired position at atreatment site, with leads 118 extend to another position either insideor outside the patient's body.

Instead of directly coupling the flexible probe to the surgical needle,a line (e.g., a suture) may be coupled to the proximal end of thesurgical needle and drawn into the treatment site along the path createdby the surgical needle in the tissue. One end of the line is thenattached to the flexible probe and the other end of the line is pulledto advance the flexible probe along the path through the tissue and intothe treatment site. This technique is not separately illustrated, sinceit should be apparent from an examination of FIG. 65. The line simplyserves as an intermediary element to draw the flexible probe into thetreatment site after the surgical needle has defined the path that willbe followed and has drawn the line into position to advance the flexibleprobe.

If the flexible probe is to remain at the treatment site for an extendedperiod of time, e.g., for several days or longer, it will normally benecessary to take steps that ensure the flexible probe does not moverelative to the treatment site, but instead remains fixed in the desiredposition to administer the medical treatment. Accordingly, as shown inFIGS. 64 and 66, a disk-shaped button 660 having a hollow sleeve 662extending outwardly from the center of one surface of the button isattached to the distal end of flexible probe 100. Preferably button 660is made of a biocompatible and elastomeric polymer plastic. The flexibleprobe is inserted inside hollow sleeve 662 and secured with a suture666, which compresses the hollow sleeve around the flexible probe.Button 660 may also be inverted, so that sleeve 662 extends distally ofthe button' disk-shaped surface. Alternatively, the distal end of theflexible probe may secured inside the hollow sleeve by crimping thehollow sleeve (so that friction between the inside surface of the hollowsleeve and the outer surface of the flexible probe provides theattaching force), or adhesively coupled thereto with a suitablebiocompatible adhesive. Although not shown in the drawings, sleeve 662may further alternatively be connected to the flexible probe using athreaded fastener, e.g., a set screw, or with a pin that extends throughthe sleeve and into the flexible probe. The diameter of button 660 isgreater than the diameter of flexible probe 100, so that the distal endof flexible probe 100 is prevented from moving back into tissue 656 bythe button. In addition, button 660 includes two orifices 664 disposedjust inside its outer circumference. Sutures 668 are passed through oneor both of these orifices to couple button 660 to tissue 656, preventmovement of the distal end of flexible probe 100. Alternatively, button660 may be adhesively attached to tissue 656, using a suitablebiocompatible adhesive.

Furthermore, as shown in FIG. 66, a disk-shaped button 670 having ahollow sleeve 672 extending outwardly from the center of one surface ofthe button may be attached to the proximal end of flexible probe 100.Button 670 is generally similar to and is made of the same plasticmaterial as button 660. However, since leads 118 extend from theproximal end, an opening 676 is formed in the center of button 670 andleads 118 pass through the opening and extend to a remote location.Button 670 is attached to the proximal end of flexible probe 100 using asuture 674 (or by crimping the hollow sleeve of button 670 around leads118 or flexible probe 100, or by use of a suitable adhesive). It isagain contemplated that a threaded fastener, or a pin (neither shown)may be used to secure the sleeve to the proximal end of the flexibleprobe. Button 670 is secured to adjacent tissue 656 using sutures 678that pass through orifices 664 formed in the button, adjacent itscircumference. Again, button 670 may be inverted so that its sleeveextends proximally of the button's disk-shaped surface.

By attaching either or both buttons 660 and 670 to flexible probe 100,the flexible probe is fixed in the desired position at the treatmentsite and prevented from moving. Although the figures illustrate apreferred embodiment in which disk-shaped buttons 660 and 670 areemployed, it will be apparent that objects having other shapes can beattached to one or both ends of a flexible probe to secure it in placein a desired position at a treatment site. The objects in thisembodiment preferably have at least one transverse dimension that isgreater than a cross sectional size of the flexible probe and/or besecured to the adjacent tissue to prevent movement of the flexible proberelative to the tissue inside the patient's body. Thus, instead ofdisk-shaped buttons 660 and 670, a rectangular or bar-shaped object (notshown) could be employed to achieve the same function. It is alsocontemplated that a patch of flexible material, e.g., generally likebutton 660 or 670 but more flexible and without a sleeve, may beattached to the lead or flexible probe and sutured or adhesively affixedto the surface of the tissue.

Fabricating Flexible Probes

For manufacturing flexible probes that are elongate, such as flexibleprobes 100 and 108, a plurality of strips of flexible substrate arepreferably produced from a larger flexible substrate 412, as shown inFIG. 46. In an initial prototype of the present invention, the overallouter dimensions of the flexible substrate are approximately 3.9"×4.6";however, these dimensions are not in any way limiting, since theflexible substrate can be made in almost any size desired. A pluralityof pairs of parallel conductive traces 414a and 414b are applied to thesurface of flexible substrate 412 using conventional photolithographytechniques, defining a plurality of flexible substrate strips 410 thatcan be cut from flexible substrate 412 after light emitting sources orother micro-electronic circuitry are mounted thereon. In the initialprototype of the present invention, the flexible traces comprise a layerof wire bondable soft gold electroplate about 0.00003" thick over alayer of sulfamate nickel electroplate about 0.0001" thick, over oneounce copper that is applied to the polyimide film comprising theflexible substrate. While substantially narrower conductive traces canreadily be formed, conductive traces 414a and 414b in the prototype areabout 0.025" wide and are spaced about 0.005" apart. Other techniquesfor producing conductive traces that are flexible and other materialscomprising the conductive traces can alternatively be used to make thepresent invention, as are well known in the prior art. Examples of priorart flexible circuit laminates and procedures for making the flexiblecircuit laminates and applying conductive traces are disclosed in U.S.Pat. Nos. 4,647,508 and 4,634,631 (Gazit et al.), which are assigned toRogers Corporation.

In FIG. 47, a flexible substrate strip 410 is illustrated (enlarged),wherein a plurality of spaced-apart "Xs" mark locations for mounting thelight emitting sources or other micro-electronic circuits on conductivetraces 414a and 414b. It is also contemplated that additional conductivetraces may be provided for more complex electronic circuitry, forexample, to convey signals and for interconnections, as is well known tothose of ordinary skill in the art.

A line 416 disposed in the middle of flexible strip 410 indicates wherethe strip is to be either cut or folded to create the flexible probeshown in FIG. 48. In this flexible probe, a plurality of LEDs 418 areattached to conductive traces 414a on flexible substrate 412, which iscut on line 416. The two portions of the flexible substrate are thenbonded together (back-to-back) to create a double thick flexiblesubstrate. Fly wires 420 connect terminals 424 on LEDs 418 to conductivetraces 414b. The fly wires are preferably ultrasonically bonded, but mayalternatively be soldered, or otherwise attached to terminals 424 andconductive traces 414b. Conductive epoxy 422 adherently attaches theother terminals of LEDs 418 to conductive traces 414a, as shown in FIG.49. Transparent flexible envelope 106 encloses the assembly, protectingLEDs 418 and fly wires 420 from damage as the flexible probe is flexedor bent during use.

Yet another configuration for a flexible probe 460 is illustrated inFIG. 53. In this configuration, light sources 470 (or othermicro-electronic circuitry), are mounted between conductive traces 466and 468 that are applied to the surface of flexible substrate strips462. The conductive traces are adherently secured to terminals on thelight sources (or other types of micro-electronic circuitry) byconductive epoxy layers 472, as shown in FIG. 54. A transparent,biocompatible flexible polymer envelope 464 protects the assembly andprovides additional strength. Light emitted by light sources 470 passesthrough flexible substrate strips 462 and through envelope 464.

A serpentine flexible sheet probe 480 is illustrated in FIG. 55. In thisembodiment, a pair of conductive traces 488 and 490 define twoserpentine paths that are generally equidistant from each other and areapplied to a flexible substrate 482. Leads 484 and 486 respectivelyconnect to the conductive traces so that electrical current can besupplied to energize light sources 492. As shown in FIG. 56, fly wires494 electrically couple light sources 492 to conductive traces 488. Thelight sources are also adhesively and electrically connected toconductive traces 490. The resulting flexible sheet is encapsulatedwithin an envelope of a clear biocompatible polymer material 496, asindicated by the dash lines surrounding the flexible substrate and lightsource.

Referring now to FIGS. 57 and 58, an alternative approach for coupling alight sources (or other type of electronic microcircuit) to conductivetraces 504 and 506 that are applied to a flexible substrate strip 502 isillustrated. In this approach, the light sources preferably comprise twodifferent types of LEDs 508 and 508' that emit light having differentcharacteristic wavebands, e.g., 640 nm peak and 720 nm peak,respectively. The LEDs are mounted on the flexible substrate strip,between conductive traces 504 and 506, with terminals on the LEDsdisposed immediately adjacent one of the conductive strips. Althoughonly one LED 508' is shown, it will be understood that LEDs 508alternate with LEDs 508' along the flexible substrate strip. Alternativeconfigurations for mounting the two types of LEDs are clearlycontemplated, for example, mounting two LEDs 508, followed by two LEDs508' along the flexible substrate strip, and various patterns or arraysof the different LEDs can be provided on flexible substrate sheets.

A fly wire 510 connects a terminal 514 disposed on one side of each LED508 to conductive trace 506, and a drop of conductive epoxy 512 connectsthe terminal on the opposite side of each LED 508 to conductive trace504. Alternatively, a corresponding drop of conductive epoxy may be usedin lieu of fly wire 510 to connect terminal 514 to conductive trace 506.Similarly, fly wire 510 (or a drop of conductive epoxy) connectsterminal 514 disposed on light source 508' to conductive trace 504, anddrop of conductive epoxy 512 connects the opposite side terminal oflight source 508' to conductive trace 506. Thus, the polarities of theterminals on LEDs 508 are opposite those of LEDs 508'. Consequently, fora particular polarity of voltage applied between conductive traces 504and 506, only one of the two different types of LEDs are energized toemit light at the characteristic waveband of that type of LED.Accordingly, by selecting the polarity of the voltage applied toenergize the LEDs, the waveband of LEDs 508 or 508' can be selected. Theother type of LEDs will not be energized until the applied voltagepolarity is reversed. An advantage of this configuration is that PDT canbe selectively administered with light at one of two differentwavebands. Two different photoreactive agents that absorb light at thecharacteristic wavebands of LEDs 508 and 508' will typically be appliedto the treatment site to enable the medical practitioner controlling thePDT to select the waveband that appears most effective in the treatment.Just as a plurality of chemotherapy regimens are often more effective indestroying cancerous tissue, a plurality of different wavebands mayprove more effective in PDT of abnormal tissue. The practitioner mayselect the more effective waveband or may elect to administer light atalternating wavebands to the treatment site.

Preferably, flexible substrate strip 502 is transparent to light emittedby LEDs 508 and 508'. Although not shown, this embodiment will typicallybe enclosed in a transparent biocompatible polymer envelope, just as theother embodiments described above are.

In FIG. 59, details of a flexible sheet probe 520 are illustrated. Inthis embodiment, a flexible substrate comprising a generally planar andquadrilateral-shaped sheet is provided with a plurality of conductivetraces 524 and 526, as pairs of strips that extend generally parallel toeach other across a flexible substrate 522. All of the strips comprisingconductive traces 524 are electrically connected to a lead 528, and allof the strips comprising conductive traces 526 are electricallyconnected to a lead 530. Depending upon the spacing between conductivetraces 524 and 526, the various techniques shown above can be used formounting light sources or other types of micro-electronic circuitry tothe pairs of conductive traces. After such devices are mounted andelectrically connected to the conductive traces, the flexible substrateprobe is enclosed within a transparent, biocompatible polymer envelope532.

To focus light emitted from light sources mounted on any of the flexibleprobes described above, it is contemplated that a reflector 544 can bemounted within or adjacent to each light source 542, as shown in FIG.60, to facilitate reflecting or focusing light emitted by the lightsource. In this Figure, conductive epoxy adhesively mounts light source542 and reflector 544 to conductive trace 524 and provides an electricpath between the terminal of the light source and the conductive trace.Similarly, a fly wire 548 electrically connects the other terminal ofthe light source to conductive trace 526. It is also contemplated that areflective surface can be fabricated within the light source, tofacilitate focusing light emitted by the light source.

Flexible Probe System

As noted repeatedly above, flexible probes made in accordance with thepresent invention can be used for other purposes, but are primarilydisclosed in connection with providing PDT. In FIG. 50, LEDs or othertypes of light source(s), and/or other types of micro-electroniccircuits are provided electrical current to energize the devices throughpower leads 316 from a power supply 326, which may be either remotelylocated outside the patient's body, may comprise a battery mountedon/adjacent the flexible probe or at a remote site within the patient'sbody, or may be coupled electromagnetically or through an RF signal, toan external source of power. It is also contemplated that power can besupplied from an external IR light source (not shown) producing IR lightthat passes through the cutaneous layer and is converted by an IRdetector (not shown) into electrical current supplied to the flexiblesubstrate. FIG. 50 is a block diagram generally illustrating theflexible probe system.

In FIG. 51, flexible probe 100 is shown with leads 316 that are intendedto extend outside the patient's body and thus terminate in connectors428 for direct connection to an external power supply 326. However, asnoted above, electrical power and signals can be conveyed between theflexible probe and an external device, across a cutaneous layer 452 andwithout a direct connection, as illustrated in FIG. 52. In this Figure,an LED array 436 and photodetectors 438 are mounted on a flexible probe440. The flexible probe is directly connected to a rectifier 434.Rectifier 434, an optional rechargeable battery 435, a receiver coilarray 430, a driver circuit 442, and a telemetry transmitter 444 arepreferably disposed together within the patient's body, apart from thetreatment site. Rectifier 434 is electrically connected to receiver coilarray 430 and full-wave rectifies alternating current output from thereceiver coil array, producing electrical current that may be used tocharge optional rechargeable battery 435. If rechargeable battery 435 isused, the power stored therein is subsequently supplied to the flexibleprobe to energize the light source(s), and/or other micro-electroniccircuitry mounted thereon. Receiver coil array 430 includes at least onereceiver coil (not shown) that is energized by electromagnetic or RFenergy transmitted from an external power coil 448 disposed outside thepatient's body, adjacent cutaneous layer 452, opposite receiver coilarray 430. Electrical energy is supplied to power coil 448 from a powersupply 450. The power supply is energized from a conventional 60 Hz, 120volts alternating current line (not shown).

Photodetectors 438 are included on flexible probe 440 to monitor thefluorescence by cells treated with a photoreactive agent at a treatmentsite, to determine whether additional photoreactive agent should beadded to the treatment site and/or to determine the efficacy of the PDT.The extent of such fluorescence is a function of the amount ofphotoreactive agent absorbed by abnormal cells, and if recently perfusedinto the treatment site, indicates the extent of abnormal cellsremaining. The photodetectors mounted on a second flexible probe (notshown) disposed on an opposite side of the treatment site from that atwhich a flexible probe comprising a light source can also be used tomonitor light transmission through the treatment site to determine theamount of photoreactive agent present and to monitor the efficacy of thesystem in applying the PDT.

Signals developed by photodetectors 438 are conveyed to a driver circuit442, which provides a suitable signal to drive telemetry transmitter444. In response to the drive signal, telemetry transmitter 444 producesan RF signal that is indicative of the output from the photocellsmounted on the flexible probe. The RF signal developed by telemetrytransmitter 444 is conveyed across cutaneous layer 452 to an externaltelemetry receiver 446, which indicates the level of the signal to anoperator.

For embodiments of the flexible probe in which it is preferable toprovide power for the light sources or other micro-electronic circuitsmounted on the flexible probe through electromagnetic coupling, asopposed to directly through leads that extend externally outside thepatient's body, either of two types of coils can be used, as shown inFIGS. 61 and 62. In FIG. 61, a receiver coil 552 comprises a pluralityof turns of conductive lead 554. Receiver coil 552 can be located atsome distance from the treatment site within the patient's body, and isdisposed immediately under and adjacent a cutaneous layer 550. Toprovide electrical energy to the flexible probe disposed at thetreatment site, a transmitter coil 556 comprising a number of turns of aconductive lead 558 that is connected to an external power supply (notshown in FIG. 61) is disposed on the outer surface of cutaneous layer550, immediately adjacent receiver coil 552. An alternating currentapplied by the external power supply develops an electromagnetic fieldin transmitter coil 556 that couples to receiver coil 552, causing acorresponding alternating current to flow in the receiver coil. Thisalternating current is rectified using a full wave rectifier (such asrectifier 434 shown in FIG. 52), which may be included within theflexible probe, or alternatively, disposed at receiver coil 552.

In a related scheme, a transmitter coil 580 comprising a ferrite core582 (or a core of another material having a relatively high magneticpermeability) that is generally "C"-shaped is coupled through leads 558to an external power supply (not shown), which supplies an alternatingcurrent to helical conductive coils 584 that are wrapped around aferrite core 582. The alternating current flowing through conductivecoils 584 develops an electromagnetic field that is coupled to areceiver coil 590. Receiver coil 590 is disposed immediately oppositetransmitter coil 580, inside the patient's body, under cutaneous layer550. Receiver coil 590 also comprises a C-shaped ferrite core 592,around which is helically coiled a conductor 594, which is coupled toleads 554 to convey electrical current to the remotely located flexibleprobe that is disposed at the treatment site within the patient's body.Transmitter coil 580 and receiver coil 590 are oriented with theirrespective ferrite cores 582 and 592 aligned, so as to maximize fluxlinkage between the ferrite cores. These coils are substantially moreefficient at transferring electromagnetic energy than transmitter coil556 and receiver coil 552, since the latter are limited by therelatively low magnetic permeability of air rather than the much greatermagnetic permeability of the ferrite cores.

It is contemplated that various other configurations and arrays oftransmitter and receiver coils can be used to supply power to energizethe electronic components inside the patient's body and mounted on theflexible probe. It is also contemplated that the receiver coil can bemounted on the flexible probe in those cases where the treatment site isdisposed immediately adjacent cutaneous layer 550.

FIG. 63 illustrates a panel 604 of infrared LEDs 606 that is disposedagainst the external surface of cutaneous layer 550. Infrared LEDs 606are energized with electrical current from the external power supplythrough leads 558. Immediately adjacent panel 604, inside cutaneouslayer 550, is disposed a panel 600 of infrared sensitive photovoltaiccells 602. In response to the infrared light received from panel 604,photovoltaic cells 602 produce an electrical current that is supplied tothe flexible probe (or a storage battery) through leads 554.

Although the present invention has been described in connection with thepreferred form of practicing it, those of ordinary skill in the art willunderstand that many modifications can be made thereto within the scopeof the claims that follow. Accordingly, it is not intended that thescope of the invention in any way be limited by the above description,but instead be determined entirely by reference to the claims thatfollow.

The invention in which an exclusive right is claimed is defined by thefollowing:
 1. A method for implanting and fixing a flexible probe in adesired position at a treatment site within a patient's body, comprisingthe steps of:(a) providing a flexible probe that comprises an elongatestrip having sufficient flexibility to sustain deformation and bendingwithout damage; (b) attaching the strip to a surgical needle; (c)forcing the surgical needle through tissue to the treatment site withinthe patient's body, so that the strip comprising the flexible probe isdrawn into the tissue by the surgical needle, along a path followed bythe surgical needle; (d) once the strip is implanted with the surgicalneedle in the desired position at the treatment site, disconnecting thesurgical needle from the strip; (e) withdrawing the surgical needle fromthe tissue, leaving the strip disposed in the desired position withinthe patient's body to administer the medical treatment to the treatmentsite; (f) securing one end of the strip to a first object, said firstobject serving to anchor the strip in the desired position at thetreatment site, preventing movement of the strip relative to thetreatment site; and (g) securing a second object to another end of saidstrip after the strip is disposed at the desired position, said secondobject including a sleeve that slips over the strip.
 2. The method ofclaim 1, further comprising the step of securing the first object to atissue surface in the patient's body.
 3. The method of claim 1, whereinsaid second object further serves to anchor the strip in the desiredposition at the treatment site, preventing movement of the striprelative to the treatment site.
 4. The method of claim 1, wherein thesecond object includes a lead that is coupled to the strip.
 5. Themethod of claim 1, wherein the steps of securing the second objectcomprises one of the steps of: crimping the sleeve of the second objectabout the strip, adhesively connecting the second object to the strip,connecting the second object to the strip with a threaded fastener,connecting the second object to the strip with a pin that extendsthrough the sleeve and into the strip, and suturing the second object tothe strip.
 6. The method of claim 1, wherein the step of forcing thesurgical needle includes one of the steps of: grasping the surgicalneedle with a needle holder, and pulling the surgical needle into thedesired position with forceps.
 7. A medical procedure for implanting andstabilizing a flexible probe at a desired position within a patient'sbody, said flexible probe being used for effecting a light therapy at atreatment site proximate the desired position, comprising the stepsof:(a) providing a strip of a flexible substrate on which is disposed alight source for effecting the light therapy, said strip having across-sectional dimension, and a length, said length of the strip beingsubstantially greater than its cross-sectional dimension; (b) coupling adistal end of the strip to a pointed instrument; (c) forcing the pointedinstrument through tissue in the body of the patient, so that thepointed instrument draws the strip after it into the desired position atthe treatment site; (d) decoupling the strip from the pointedinstrument; and (e) withdrawing the pointed instrument from thepatient's body, leaving the strip and the light source disposed at thedesired location to administer the light therapy to the treatment site.8. The method of claim 7, further comprising the step of securing thestrip so that it does not move from the desired position.
 9. The methodof claim 8, wherein the step of securing comprises the step of couplingan object having a relatively larger cross-sectional size than the stripto at least one end of the strip.
 10. The method of claim 8, wherein thestep of securing comprises the step of coupling an object having arelatively larger cross-sectional size than the strip to both ends ofthe strip.
 11. The method of claim 8, wherein the step of securingcomprises the step of coupling the strip using one of an adhesive, acrimped sleeve, a threaded fastener, a pin, and a suture.
 12. The methodof claim 7, wherein the pointed instrument comprises a surgical needle.13. The method of claim 7, further comprising the steps of passing alead from the strip through an opening in an object; and fastening theobject to the lead to secure the strip in the desired position, saidlead extending proximally beyond the object to a different location. 14.The method of claim 7, wherein a distal end of the strip is secured toan object that is disposed against a tissue surface to prevent movementof the strip from the desired position at the treatment site. 15.Apparatus adapted for administering a light therapy to a treatment sitedisposed within a patient's body, comprising:(a) a flexible strip havinga width and a length, said width being substantially less than saidlength of the flexible strip, a light source being disposed on theflexible strip for effecting the light therapy at the treatment site;(b) a pointed instrument for defining a path through the tissue in thepatient's body, said path being used for delivering the flexible stripto the treatment site in the patient's body; and (c) means for drawingthe flexible strip behind the pointed instrument along the path throughtissue in the patient's body so that the flexible strip is disposed in adesired position at the treatment site, and so that the light source isthereby enabled to administer the light therapy to the treatment site.16. The apparatus of claim 15, further comprising an object attachableto the flexible strip, said object being attached to at least one end ofthe flexible strip after the flexible strip is introduced to thetreatment site, to secure the flexible strip in the desired position,preventing the flexible strip from moving away from the desiredposition.
 17. The apparatus of claim 15, wherein the object includes asleeve that is sized to fit over an end of the flexible strip and to besecured thereto.
 18. The apparatus of claim 17, wherein the sleeve issecured to the flexible strip by one of a crimp of the sleeve, anadhesive, a threaded fastener, a pin that extends through the sleeve,and a suture.
 19. The apparatus of claim 17, wherein the object includesan opening, and wherein the flexible strip is attached to a lead thatextends from the flexible strip to another location, said lead passingthrough the opening in the object and being secured to the object toprevent movement of the flexible strip away from the desired position.20. The apparatus of claim 15, wherein the pointed instrument comprisesa surgical needle.
 21. A method for implanting and fixing a flexibleprobe in a desired position at a treatment site within a patient's bodyto deliver a light therapy to the treatment site, comprising the stepsof:(a) providing a flexible probe that comprises an elongate striphaving sufficient flexibility to sustain deformation and bending withoutdamage, said flexible strip including a plurality of light sources foreffecting the light therapy; (b) forcing a pointed instrument throughtissue to the treatment site within the patient's body, creating a paththrough the tissue; (c) drawing the strip comprising the flexible probeinto the tissue, along the path followed by the pointed instrument; and(d) once the strip is implanted at the treatment site, administering thelight therapy to the treatment site with the plurality of light sources.22. The method of claim 21, wherein a line is coupled to the pointedinstrument so that the line is drawn through the tissue behind thepointed instrument and extends behind the pointed instrument along thepath followed thereby, wherein the step of drawing the strip comprisesthe step of coupling the strip to the line and pulling the line alongthe path through the tissue to advance the strip into the treatmentsite.
 23. The method of claim 21, wherein the strip is coupled to thepointed instrument and is drawn into the treatment site as the pointedinstrument is advanced.
 24. A method for implanting and fixing aflexible probe in a desired position at a treatment site within apatient's body, comprising the steps of:(a) providing a flexible probethat comprises an elongate strip having sufficient flexibility tosustain deformation and bending without damage; (b) attaching the stripto a surgical needle; (c) forcing the surgical needle through tissue tothe treatment site within the patient's body, so that the stripcomprising the flexible probe is drawn into the tissue by the surgicalneedle, along a path followed by the surgical needle; (d) once the stripis implanted with the surgical needle in the desired position at thetreatment site, disconnecting the surgical needle from the strip; (e)withdrawing the surgical needle from the tissue, leaving the stripdisposed in the desired position within the patient's body to administerthe medical treatment to the treatment site; (f) securing one end of thestrip to a first object, said first object serving to anchor the stripin the desired position at the treatment site, preventing movement ofthe strip relative to the treatment site; and (g) securing a secondobject to another end of said strip after the strip is disposed at thedesired position, said second object including a sleeve that slips overthe strip, said step of securing including one of the steps of: crimpingthe sleeve of the second object about the strip, adhesively connectingthe second object to the strip, connecting the second object to thestrip with a threaded fastener, connecting the second object to thestrip with a pin that extends through the sleeve and into the strip, andsuturing the second object to the strip.